Seminars in Cancer Biology, Год журнала: 2023, Номер 94, С. 21 - 33
Опубликована: Июнь 5, 2023
Язык: Английский
Journal of Experimental & Clinical Cancer Research, Год журнала: 2023, Номер 42(1)
Опубликована: Март 22, 2023
Metastases are the major cause of cancer-related morbidity and mortality. By time cancer cells detach from their primary site to eventually spread distant sites, they need acquire ability survive in non-adherent conditions proliferate within a new microenvironment spite stressing that may severely constrain metastatic process. In this study, we gained insight into molecular mechanisms allowing an anchorage-independent manner, regardless both tumor-intrinsic variables nutrient culture conditions.3D spheroids derived lung adenocarcinoma (LUAD) breast were cultured either nutrient-rich or -restricted conditions. A multi-omics approach, including transcriptomics, proteomics, metabolomics, was used explore changes underlying transition 2 3D cultures. Small interfering RNA-mediated loss function assays validate role identified differentially expressed genes proteins H460 HCC827 LUAD as well MCF7 T47D cell lines.We found cultures is associated with significant expression involved metabolic reprogramming. particular, observed tumor spheroid growth implies overexpression ALDOC ENO2 glycolytic enzymes concomitant enhanced consumption glucose fructose production lactate. Transfection siRNA against determined reduction lactate production, viability size produced by H460, HCC827, MCF7, lines.Our results show survival supported drive metabolism towards production. Notably, finding valid for all lines have analyzed different environmental broader Validation mechanism other origin will be necessary broaden types. Future vivo studies assess metastasis.
Язык: Английский
Процитировано
26
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Фев. 13, 2024
Abstract Immune checkpoint blockade (ICB) has shown considerable promise for treating various malignancies, but only a subset of cancer patients benefit from immune inhibitor therapy because evasion and immune-related adverse events (irAEs). The mechanisms underlying how tumor cells regulate cell response remain largely unknown. Here we show that hexokinase domain component 1 (HKDC1) promotes in CD8 + T cell-dependent manner by activating STAT1/PD-L1 cells. Mechanistically, HKDC1 binds to presents cytosolic STAT1 IFNGR1 on the plasma membrane following IFNγ-stimulation associating with cytoskeleton protein ACTA2, resulting phosphorylation nuclear translocation. inhibition combination anti-PD-1/PD-L1 enhances vivo antitumor liver models male mice. Clinical sample analysis indicates correlation among expression, phosphorylation, survival hepatocellular carcinoma treated atezolizumab (anti-PD-L1). These findings reveal role regulating coupling activation, providing potential strategy enhance responses.
Язык: Английский
Процитировано
17
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Апрель 5, 2024
Abstract For decades, great strides have been made in the field of immunometabolism. A plethora evidence ranging from basic mechanisms to clinical transformation has gradually embarked on immunometabolism center stage innate and adaptive immunomodulation. Given this, we focus changes immunometabolism, a converging series biochemical events that alters immune cell function, propose roles played by diversified metabolic derivatives enzymes, emphasize key metabolism-related checkpoints distinct types, discuss ongoing upcoming realities treatment. It is expected future research will reduce current limitations immunotherapy provide positive hand responses exert broader therapeutic role.
Язык: Английский
Процитировано
14
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 22, 2024
Abstract The question of how metabolism impacts development is seeing a renaissance [1, 2]. How exerts instructive signaling functions one the central issues that need to be resolved. We tackled this in context mouse embryonic axis segmentation. Previous studies have shown changes carbon impact Wnt [3–6] and period segmentation clock [7], which controls timing Here, we reveal glycolysis tunes an anti-correlated manner: higher glycolytic flux slows down clock, vice versa. Transcriptome gene regulatory network analyses identified specifically transcription factor Tcf7l2, previously associated with increased risk for diabetes [8, 9], as potential mechanisms underlying flux-dependent control period. Critically, show deletion antagonist Dkk1 rescued slow phenotype caused by glycolysis, demonstrating instructs In addition, demonstrate metabolic entrainment clock: periodic levels glucose or sentinel metabolite fructose 1,6-bisphosphate (FBP) synchronize oscillations. Notably, FBP pulses first entrained oscillations subsequently Notch hence conclude has immediate, specific effect on signaling. Combined, our work identifies glycolysis-FBP-Wnt developmental timing, highlighting role development.
Язык: Английский
Процитировано
11
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 2, 2025
Язык: Английский
Процитировано
2
Molecular Cell, Год журнала: 2025, Номер 85(2), С. 262 - 275
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
2
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Фев. 4, 2025
Язык: Английский
Процитировано
2
Nature Metabolism, Год журнала: 2025, Номер unknown
Опубликована: Янв. 6, 2025
Язык: Английский
Процитировано
1
Biochemistry, Год журнала: 2025, Номер unknown
Опубликована: Янв. 22, 2025
Glutamine synthetase (GS) is a ubiquitous enzyme central to nitrogen metabolism, catalyzing the ATP-dependent formation of glutamine from glutamate and ammonia. Positioned at intersection metabolism with carbon activity GS subject sophisticated regulation. While intricate regulatory pathways that govern Escherichia coli were established long ago, recent work has demonstrated homologues are controlled by multiple distinct patterns, such as metabolite induced oligomeric state in archaeal 2-oxoglutarate. Such was enabled large part advances cryo-electron microscopy (cryoEM) allowed greater structural access this complex, assessment heterogeneous states protein-interactor-GS complexes. This perspective highlights understanding regulation, focusing on dynamic interplay between its state, binding, protein interactors. These interactions modulate activity, influencing cellular processes assimilation, stress responses. Furthermore, we explore emerging concept "moonlighting" functions, revealing roles palmitoylation, cell cycle ion channel modulation. diverse functions highlight newfound versatility beyond primary catalytic role suggest complex health disease warrant further study.
Язык: Английский
Процитировано
1
Advanced Science, Год журнала: 2025, Номер unknown
Опубликована: Янв. 30, 2025
Abstract Cancer cells cope with oxidative stress for their proliferation and metastasis by equipping antioxidant systems, among which the enzymes peroxiredoxins (PRDXs) play crucial roles. However, whether PRDXs exhibit nonenzymatic functions remains unclear. Here, it is shown that 1‐cysteine PRDX (PRDX6) upregulates nicotinamide N ‐methyltransferase (NNMT) to promote growth of ovarian cancer cells, independently PRDX6's enzymatic activities. Mechanistically, PRDX6 interacts NNMT prevent its binding E3 ubiquitin ligase tripartite‐motif protein 56 (TRIM56), leading inhibition ubiquitination at lysine 23 210 suppression subsequent proteasomal degradation. In addition, PRDX6‐mediated upregulation activates mitogen‐activated kinase (MAPK) signaling, thereby promoting cells. Notably, overexpression associated higher levels in human tissues predictive poor prognosis patients. Overall, findings illustrate a critical oncogenic mechanism enzyme progression beyond mechanisms.
Язык: Английский
Процитировано
1